Volume 1, Number
2, December 1998
Pages 71-79
J.H. Dowson, C.Q. Mountjoy, M.R. Cairns, H. Wilton-Cox and W.
Bondareff
Lipopigment
changes in Purkinje cells in Alzheimer's disease
Abstract: Cerebellar tissue was examined from 22 patients
with Alzheimer's disease (AD) and from an age-matched group of 20
non-diseased subjects. Intraneuronal lipopigment in the bodies of
1344 Purkinje cells (PCs) (32 per brain) was identified by
fluorescence microscopy. The mean total area (per PC) of the
outlines of discrete regions of lipopigment in a PC perikaryon for
the AD-related group of PCs was significantly greater than the mean
for the comparison group (p < 0.001). Also, the two groups of PCs
showed significant (< 0.05) differences in the mean number (per PC)
of discrete regions of lipopigment in 11 size categories. The
findings indicate a lysosomal abnormality in PCs in AD. The pattern
of size distribution of lipopigment in PCs differed from that
previously-reported for neurons of the frontal cortex. These
differences may be associated with the absence of senile plaques and
the presence of "diffuse" amyloid plaques in the cerebellum in AD.
Pages 81-89
Ann M. Kazee and Eileen M. Johnson
Alzheimer's disease pathology in
non-demented elderly
Abstract: The purpose of this study was to quantitate the
extent of neuropathological lesions (neurofibrillary tangles and
senile plaques) characteristic of Alzheimer's disease in cognitively
intact elderly control subjects. The subjects included twenty-six
elderly individuals who were autopsied at a university-based
Alzheimer's Disease Center. The mean age at autopsy was 78 years
(range 51-99 years); there were 15 males and 11 females. All of
these control subjects had a few neurons containing neurofibrillary
tangles in the hippocampus, but no neurofibrillary tangles in the
neocortex. Twelve of the 26 subjects (46%) had some senile plaques
in the neocortex, while fourteen (54%) did not. Six subjects (23%)
had substantial numbers of senile plaques in the neocortex. Neither
the number of neurons containing neurofibrillary tangles nor the
number of senile plaques correlated with age in these subjects.
Possible conclusions are that there are many elderly individuals
with incipient Alzheimer's Disease, or that one can have some degree
of these lesions and still be cognitively normal. These data point
out the need to have better pathological markers of the disease
process and better diagnostic criteria to define Alzheimer's
Disease.
Pages 91-105
Garth Bissette, Larry Cook, Wayne Smith, Kenneth C. Dole, Barbara
Crain and Charles B. Nemeroff
Regional
neuropeptide pathology in Alzheimer's disease:
corticotrophin-releasing factor and somatostatin
Abstract: Background. The neuropeptides most
consistently reported to be altered in Alzheimer's disease are
corticotrophin-releasing factor and somatostatin (somatrotrophin-release
inhibiting factor), although this has been previously assessed in a
limited number of brain regions. Methods. In order to
comprehensively characterize the involvement of these two
anatomically distinct neuropeptide systems in Alzheimer's disease
and to determine if they are equally involved in the associated
pathology, we measured the concentration of corticotrophin-releasing
factor and somatostatin in post-mortem brain tissue.
Radioimmunoassay of 24 cortical and 13 sub-cortical brain regions
from 16 cases of neuropathologically confirmed AD and 9
non-Alzheimer's disease controls were performed and significant
differences in groups regional neuropeptide concentrations were
sought using the Student Newman-Keuls test after ANOVA. Results.
Comparison of group mean regional neuropeptide concentrations
revealed several brain regions where both peptides were decreased in
Alzheimer's disease and some regions where only one of the two
peptides were decreased, while still other regions exhibited no
changes in either peptide. These changes were principally found in
frontal and temporal cortex, with few subcortical regions exhibiting
pathologic changes in peptide concentration. Regional peptide
content was correlated among peptides and with duration of dementia
in several brain regions. Conclusions. These data support the
hypothesis that the somatostatin- and corticotrophin-releasing
factor containing neurons are pathologically involved in AD and that
the involved neurons are limited to specific areas of the brain.
Pages 107-118
A. Salehi, C.W. Pool, M. Mulder, R. Ravid, N.K. Gonatas and D.F.
Swaab
Activity of
hippocampal CA1 neurons in Alzheimer's disease is not affected by
the presence of adjacent neuritic plaques
Abstract: Alzheimer's disease (AD) is neuropathologically
characterized by neuritic plaques (NPs) and neurofibrillary tangles
and functionally be a decreased metabolic rate of neurons. Our
previous studies showed that in brain areas which are extensively
affected by plaques and tangles, i.e., the CA1 area of the
hippocampus and the hypothalamic tuberomamillary nucleus, neuronal
protein synthetic ability is significantly lower in AD patients than
in controls. However, the presence of tangles as shown by Bodian
staining appeared not to be directly related to decreased protein
synthetic ability of neurons. In order to study to what extent the
metabolic function of neurons might be affected by the other
neuropathological hallmark of AD, i.e., NPs, which are presumed to
contain neurotoxic compounds, we studies eight severely demented AD
patients matched for the ApoE genotype (ApoE 3/3). Using an image
analysis system, the size of the neuronal Golgi apparatus (GA) and
of the cell profile area was measured as a parameter for protein
synthetic activity in the CA1 area of these patients. NPs were
stained by Bodian, and subsequently the distance of each neurons
with immunostained GA to the nearest NP was measured. Our results
showed that neither NP density nor the distance between NPs and
neurons correlated with the protein synthetic ability of neurons as
judged by the size of the GA. Based on these results we suggest
that in AD the presence of NPs and decreased neuronal protein
synthetic ability are basically two independent phenomena.
Pages 119-134
D. Etiene, J. Kraft, N. Ganju, T. Gomez-Isla, B. Gemelli, B.T. Hyman,
E.T. Hedley-Whyte, J.R. Wands and S.M. de la Monte
Cerebrovascular pathology
contributes to the heterogeneity of Alzheimer's disease
Abstract: Heterogeneous pathology in Alzheimer's Disease (AD) is
due to variability in the nature and severity of lesions, overlap with
other neurodegenerative diseases such as Parkinson's disease, or the co-existence
of cerebrovascular disease. In the MGH-ADRC autopsy archives, remote
cerebral infarcts (CVA) were reported in 30% of the otherwise uncomplicated
AD cases. To determine the potential significance of cerebrovascular
lesions in relation to AD, the relative densities (CERAD grading criteria)
of Bielschowsky-stained AD lesions and Aß-amyloid immunoreactive plaques
were compared among cases of AD+CVA (N = 52), AD (N = 48), aged controls
(NC, N =9), and aged controls with AD lesions (ADC, N = 8). The
prevalence of the ApoE e4 allele was also determined for each group.
This study demonstrated: 1) higher densities of Bielschowsky-stained plaques
in AD, AD+CVA, and ADC than in NC (P < 0.0001); 2) more abundant neurofibrillary
tangles in AD relative to all other groups (P < 0.0005), and in AD+CVA
and ADC relative to NC (P < 0.05); and 3) increased densities of Aß-amyloid-immunoreactive
plaques in AD relative to AD+CVA (P = 0.0003). In AD+CBA, cerebral
vascular lesions consisting of remote microscopic cortical and subcortical
white matter infarcts, ischemic lesions, and leukoaraiosis were consistently
distributed in structures typically damaged by AD neurodegeneration, as
well as in the basal ganglia. The ApoE e4 allele was more prevalent
in the AD+CVA (70%) than in the AD (58%) group (P = 0.05). Since
the AD and AD+CVA groups had similar degrees of dementia, the results
suggest that cerebral vascular lesions in regions typically destroyed
by AD may contribute to the clinical manifestations of AD.
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